The inhibition of cancer cell stickiness, a model for investigation of platelet aggregation inhibitors in vivo. Effect of the sulfonyl urea derivatives, glibenclamide, gliclazide, and HB180, as well as the carboxylic acid derivative, meglitinide.
Employing the test model which we developed for the investigation of platelet adhesiveness and aggregation in vivo, experiments demonstrated that the sulfonyl urea derivatives, glibenclamide, gliclazide, and HB 180, as well as the carboxylic acid derivative, meglitinide, are able to inhibit, in a dose-dependent relationship, the adherence of i.v. injected Walker-256-carcinosarcoma cells to the vascular endothelium of the rat mesentery, as well as to reduce significantly the rate of instantly occurring terminal tumor cell embolism of the lung. Since venous blood platelet count in surviving animals is inversely proportional to the number of the tumor cells which adhere to the vascular endothelium, one can deduce that tumor cell embolism is an immediate result of a massively occurring disseminated intravascular coagulation (DIC) which may be induced by i.v. injection of thromboplastic active carcinosarcoma cells and leads primarily to a drastic platelet count reduction. All four substances inhibit this platelet count reduction as well as the directly correlated tumor cell embolism mortality rate in a linear dose-dependent fashion. Their action can therefore be explained as being mediated via an inhibition of platelet adhesion and aggregation to the circulating tumor cells. Our proof of platelet aggregation in vivo correlates with the results obtained by Klaff et al. (1979), as far as a normalization of the pathologically increased platelet aggregation tendency in vitro in diabetics following 4-6 weeks of therapy with the sulfonyl urea derivatives glibenclamide and gliclazide.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002279:Carcinoma 256, Walker / Q000503:physiopathology*; D002449:Cell Aggregation / Q000187:drug effects*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology; D005907:Gliclazide / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D051381:Rats; D011919:Rats, Inbred Strains; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D001549:Benzamides; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C034427:HB 180; C030516:meglitinide; D005907:Gliclazide; D005905:Glyburide